This proposal requests expanded support for a pioneering predoctoral training program in systems biology. The Harvard Ph.D. Program in Systems Biology attracts unusually adventurous and analytically confident graduate students, with a demonstrated determination to cross disciplines. Our central goal is to help these students identify biological questions to which an interdisciplinary approach can provide uniquely satisfying answers, and to prepare them to identify and address such questions independently in their future careers. The Program draws on the intellectual and practical resources of the entire Harvard scientific community to help students develop a broad, rigorous and creative approach to solving challenging problems in biology and medicine. A two-part Preliminary Qualifying Exam is central to our approach. Part 1 requires the student to propose a quantitative, computational, or theoretical approach to solving a biological problem. This tests the student's ability to conceive, articulate, and exercise quantitative and theoretical ideas and methods as applied to questions in biology. This section of the exam demands creativity and thoughtful analysis of what theory and computation can offer, as well as general knowledge about biology. Part 2 evaluates the student's plan for dissertation research and understanding of experimental logic and methods. Our students enter the Program with a wide variety of backgrounds. Students may take any of a range of science courses offered by Harvard or MIT (through cross-registration). The first year student faculty advisors work with entering students individually to help them determine which courses will best complement their existing training, and to help them to identify potential rotation labs. Five courses on different aspects of systems biology are offered by Program faculty. In addition all students are required to take a course on communication that culminates in writing a fellowship proposal, and a course on biomedical research ethics. Our program aims to educate students in the current state of the art in systems biology, and to encourage them to reach higher, expanding the use of systems biology approaches in biology and medicine. Our students have published many high-quality papers on systems ranging from bacterial pathogens to humans. An average student graduating from the program will have published 3.5 papers, of which 2 are first-author papers. We believe that the students we attract and the mentoring that we give them are both outstanding, and that we have the ability to recruit additional exciting students into the Program who could benefit greatly from the opportunities we can offer them. We are therefore requesting an increase from 6 training slots to 8 for this funding cycle. Students will be funded in their first and second year of graduae studies.